The molecular Genetics of the fruit fly, Drosophila melanogaster, have allowed an unrivaled description of the genetic mechanisms controlling the establishment of the embryonic body plan. Moreover, studies of genes significant to segmentation and developmental commitments that were identified by genetic analysis in Drosophila have led to an appreciation of the importance of their homologs during human development. However, flies are very advanced with respect to their specialized development. The proposed project will examine the genetic control of segmentation in the red flour beetle, Tribolium castaneum. This species shows relatively primitive embryological development, and offers demonstrated utility for molecular and developmental studies of embryogenesis. Its greatest advantage is the possibility of isolating mutations allowing functional studies of important genes and the recognition of those not described in Drosophila. Studies of the homeotic selector genes, the segmentation gap genes, hunchback and Kruppel, and the segment-polarity gene engrailed are already underway.In this project, homologs of segmentation genes in the pair-rule (even-skipped, hairy and runt) and segment-polarity (Wingless) classes will be molecularly cloned and their temporal/spacial patterns of expression during embryogenesis determined. Selected genes will be located by RFLP mapping, and mutant alleles will be generated. Mutations in genes necessary for normal segmentation will be isolated directly, allowing the recognition of novel functions. The functional significance and interaction of these genes will be studied by describing the lethal syndromes of single and multiple mutants, and by assessing the effect of mutations on the patterns of expression of other genes. The study will result in better appreciation of embryonic mechanisms important to insects in general, and also has the potential to suggest control strategies for agricultural pests and disease vectors and to identify novel genes important to early human development.